Microbicide product development has become an essential focus in the HIV prevention field. These products are applied prior to sexual intercourse to prevent HIV acquisition have the potential to become the first line of defense in combating the spread of HIV. However, acceptable formulations of microbicide candidates are required if this approach is to succeed. Although a number of potential microbicide drug candidates have been identified, little attention has been given to product formulation. The reverse transcriptase inhibitors tenofovir (TFV) and UC781 have significant activity against HIV. Although gel vaginal products are currently being evaluated in the clinic for these candidates, ultimately, it may be necessary to develop multiple dosage platforms to provide users with products that they can readily use within the constraints of their social environment, personal choice, and environmental conditions. In this program, quick dissolve vaginal films will be developed for TFV, UC781, and a combination ofthe two. Film dosage forms are easily applied, are inexpensively manufactured, are easily transportable, and eliminate the need for product applicators. This project also addresses a formulation issue with UC781 which impacts all dosage form types. UC781 has very low aqueous solubility and undergoes oxidative degradation. This attribute makes formulation difficult. In this project, the use of complexation and co-crystallization as a means for solubilization and stabilization of UC781 will be explored. Successful solubilization/stabilization ofthis compound will provide a basis for more efficient incorporation of UC781 into a dosage form. Ultimately a panel of dispersed film and gel formulations and formulations implementing these delivery strategies will be evaluated in a thorough product comparison. The most promising formulations will be advanced to monkey safety and efficacy testing in Project 2 and ultimately scaled up through Core C and brought forward to human studies in Projects 3 and 4. This project also includes evaluation of the potential for the use of melt extrusion which provides certain benefit from a manufacturing and economic standpoint, for the production of TFV and UC781 film products. Manufacture by hot melt extrusion will be compared with aqueous solvent casting technology.